Agricultural practices profoundly influence soil microbial populations and physicochemical properties, vital for crop growth and quality. This study aims to explore the impact of diverse agrochemical applications on soil microbial dynamics, physicochemical properties, and maize yield and proximate properties. Topsoil samples, collected at depths of 1 to 15 cm, were transported to Jimma University for maize cultivation. Over 120 days, soil and maize samples were collected at specified intervals for analysis, including soil pH, microbial populations, and nutrient content. Statistical analysis using one-way ANOVA (p < 0.05) was conducted. Soil bacterial and fungal populations were measured on days 5, 10, 20, 40, 80, and 120. The highest total mesophilic bacterial count (TMBC) was in compost-treated pots (G) and the lowest in those receiving macronutrient fertilizers and glyphosates (B). The highest total mesophilic fungal count (TMFC) was in pots with glyphosates and compost (F), and the lowest was in pots treated with macronutrient fertilizers and glyphosates (B). Pots treated with macronutrient fertilizers and glyphosates (B), macronutrient fertilizers (A), and micronutrient fertilizers (C) showed the lowest Fe and Zn levels. Maize in pots treated with macronutrient fertilizer combined with glyphosate (B) exhibited the lowest protein, fats, and carbohydrates. Notably, compost-treated soils showed the highest bacterial and fungal counts, Fe, and Zn concentrations, while micro-mineral fertilizer combined with glyphosate (B) depleted the soil. Agrochemical treatments negatively affected maize yield quality, indicating complex treatment-related changes in soil parameters.